ASCO15: AdV-Tk gene therapy + surgery could extend survival for glioblastoma patients by 8 months

David Baskin, a neurosurgeon from the Houston Methodist Neurological Institute (TX, USA), has presented his preliminary data from the Phase II trial of AdV-Tk gene therapy combined with surgical resection for glioblastoma patients at the annual meeting of American Society of Clinical Oncology (held 29 May–2 June). As the most common and one of the most difficult to treat brain cancer subtypes, the results shed light on the potential of AdV-Tk + surgery as a future treatment strategy.

AdV-Tk is a gene-mediated cytotoxic immunotherapy that primarily works by killing cancer cells directly. It also releases proteins that cause a hyperstimulation of the immune system to enable the activation of immune pathways, which indirectly kills cancer cells for months to years later.

In the multicenter open-label study, the outcomes of 48 patients who had completed the experimental therapy regime of AdV-Tk (based on mediated herpes simplex virus) as well as surgical resection from 2006–2010, were compared with outcomes of 134 patients who only received surgical resection.

All patients enrolled on the study had received no prior radiation treatment and were considered to be surgery candidates. During resection – when as much cancerous tissue as possible was removed – the AdV-Tk gene therapy was injected ten times at the site of resection. The antiviral drug valacyclovir was then administered orally for 2 weeks after resection, and patients subsequently received radiation therapy and chemotherapy as tolerated.

Median survival increased from 13.5 to 17.1 months (3.6 months) and there was a 27% increase in overall survival at the end of 5 years. For patients who underwent aggressive surgical resection, a significant improvement in survival was seen, with an increase of 57 to 67% survival at 1 year, 22 to 35% at 2 years and then 8 to 19% at 3 years. Overall, the improved survival was reported to be approximately 8 months.

Baskin commented: “These results are far better that what we can now achieve with our present standard of care for treatment of patients with glioblastoma.”

The ground-breaking findings will lead to further research on a larger scale. While glioblastoma patients currently face a median survival average of 15 months and poor quality of life in the last 5 months, ADV-Tk + aggressive surgical resection could provide a big step forward in improving current therapeutic strategies for glioblastoma patients.

Sources: Aguilar LK, Wheeler LA, Manzanera AG et al. Phase II multicenter study of gene mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. J. Clin. Oncol. 33, (2015) [ASCO 2015 abstract] http://abstracts.asco.org/156/AbstView_156_152063.html; Houston Methodist Hospital Research Institute press release via Newswise